Interleukin-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine.
Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in the ceca of streptomycin-pretreated mice that involves T-cell-dependent induction of gamma interferon (IFN-gamma), interleukin-22 (IL-22), and IL-17 expression (genes Ifn-gamma, Il-22, and Il-17, respectively). We investigated here the role of IL-23 in initiating these inflammatory responses using the streptomycin-pretreated mouse model. Compared to wild-type mice, the expression of IL-17 was abrogated, IL-22 expression was markedly reduced, but IFN-gamma expression was normal in the ceca of IL-23p19-deficient mice during serotype Typhimurium infection. IL-23p19-deficient mice also exhibited a markedly reduced expression of regenerating islet-derived 3 gamma, keratinocyte-derived cytokine, and reduced neutrophil recruitment into the cecal mucosa during infection. Analysis of CD3(+) lymphocytes in the intestinal mucosa by flow cytometry revealed that alphabeta T cells were the predominant cell type expressing the IL-23 receptor in naive mice. However, a marked increase in the number of IL-23 receptor-expressing gammadelta T cells was observed in the lamina propria during serotype Typhimurium infection. Compared to wild-type mice, gammadelta T-cell-receptor-deficient mice exhibited blunted expression of IL-17 during serotype Typhimurium infection, while IFN-gamma expression was normal. These data suggested that gammadelta T cells are a significant source, but not the sole source, of IL-17 in the acutely inflamed cecal mucosa of mice. Collectively, our results point to IL-23 as an important player in initiating a T-cell-dependent amplification of inflammatory responses in the intestinal mucosa during serotype Typhimurium infection.
Godinez
Ivan
I
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA 95616-8645, USA.
Raffatellu
Manuela
M
Chu
Hiutung
H
Paixão
Tatiane A
TA
Haneda
Takeshi
T
Santos
Renato L
RL
Bevins
Charles L
CL
Tsolis
Renée M
RM
Bäumler
Andreas J
AJ
D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D002432:Cecum / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D053759:Interleukin-23 / Q000172:deficiency / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000032:analysis; D012486:Salmonella typhimurium / Q000276:immunology*
D017252:CD3 Complex; D016207:Cytokines; D053759:Interleukin-23; D018123:Receptors, Interleukin